US2003069196A1PendingUtilityA1

Compositions and methods for the treatment and diagnosis of immune disorders

48
Assignee: MILLENNIUM PHARM INCPriority: Mar 3, 1995Filed: Dec 4, 2001Published: Apr 10, 2003
Est. expiryMar 3, 2015(expired)· nominal 20-yr term from priority
Inventors:Douglas LevinsonClare LloydSean Mccarthy
C07K 2319/00A01K 2217/00A01K 2207/15A01K 2217/075A01K 67/0275A61K 38/00A01K 2267/0393C12N 9/6467C12Q 1/6809C12N 15/8509C12N 9/6472C07K 14/70503A01K 2267/0375A01K 2267/03A01K 2217/05C07K 14/47A01K 2267/0387C07K 19/00A01K 67/0278A01K 2267/0325A01K 2267/0381A01K 2267/0368A01K 2227/105
48
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Claims

Abstract

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders, and also for the treatment of mast cell-related processes and disorders, ischemic disorders and injuries, including ischemic renal disorders and injuries. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders. Additionally, methods are provided for the diagnostic evaluation and prognosis of TH cell subpopulation-related disorders, for the identification of subjects exhibiting a predisposition to such conditions, for monitoring patients undergoing clinical evaluation for the treatment of such disorders, and for monitoring the efficacy of compounds used in clinical trials. Methods are also provided for the treatment of symptoms associated with mast cell-related processes or disorders and ischemic disorders and injuries using the genes, gene products and antibodies of the invention.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method for ameliorating a symptom of an ischemic disorder or injury in a mammal, comprising administering to the mammal a 200 gene product in an amount effective to ameliorate the symptom of the ischemic disorder or injury.  
     
     
         2 . A method for ameliorating a symptom of an ischemic disorder or injury in a mammal, comprising administering to the mammal a nucleic acid molecule encoding a 200 gene product in an amount effective to ameliorate the symptom of the ischemic disorder or injury.  
     
     
         3 . A method for ameliorating a symptom of an ischemic disorder or injury in a mammal, comprising administering to the mammal an antibody directed against a 200 gene product in an amount effective to ameliorate the symptom of the disorder.  
     
     
         4 . The method of  claim 1 ,  2 , or  3 , wherein the ischemic disorder is ischemic renal disease, or myocardial ischemia.  
     
     
         5 . The method of  claim 4 , wherein the myocardial ischemia is angina pectoris.  
     
     
         6 . The method of  claim 1 ,  2 , or  3  wherein the ischemic disorder or injury is a infarction.  
     
     
         7 . The method of  claim 6 , wherein the infarcation is a myocardial infarction, or a cortical infarction.  
     
     
         8 . The method of  claim 1 ,  2 , or  3 , wherein the ischemic injury is to a transplanted organ.  
     
     
         9 . The method of  claim 8 , wherein the transplanted organ is a kidney.  
     
     
         10 . The method of  claim 1 ,  2 , or  3 , wherein the 200 gene product is a polypeptide comprising: 
 (a) the amino acid sequence of SEQ ID NO:10,    (b) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:8,    (c) the amino acid sequence encoded by the cDNA insert of the clone  E. coli  DH10B(Zip)™ containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-O (NRRL Accession No. B-21395),    (d) the amino acid sequence of SEQ ID NO:24,    (e) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:37, or    (f) the amino acid sequence encoded by the cDNA insert of the clone feht200C. (ATCC Accession No. 69967).    
     
     
         11 . The method of  claim 1 ,  2 , or  3 , wherein the 200 gene product is a polypeptide encoded by a nucleic acid molecule which hybridizes under highly stringent conditions to the complement of: 
 (a) a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO:10,    (b) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:8,    (c) the cDNA sequence contained in the clone  E. coli  DH10B (Zip)™ containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-O (NRRL Accession No. B-21395),    (d) to the complement of a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO:24,    (e) to the complement of the nucleotide sequence of SEQ ID NO:37, or    (f) to the complement of the cDNA sequence contained in the clone feht200C. (ATCC Accession No. 69967).    
     
     
         12 . The method of  claim 2  wherein the nucleic acid molecule encoding a gene 200 product comprises: 
 (a) a nucleotide sequence which encodes the amino acid sequence of SEQ ID NO:10,  
 (b) the nucleotide sequence of SEQ ID NO:8,  
 (c) the nucleotide sequence of the cDNA insert of the clone  E. coli  DH10B (Zip)™ containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-O (NRRL Accession No. B-21395),  
 (d) a nucleotide sequence which encodes the amino acid sequence of SEQ ID NO:24,  
 (e) the nucleotide sequence of SEQ ID NO:37, or  
 (f) the nucleotide sequence of the cDNA insert of the clone feht200c (ATCC Accession No. 69967).  
 
     
     
         13 . The method of  claim 1  wherein said administering of the 200 gene product is parenteral, subcutaneous, intraperitoneal, intrapulmonary, intranasal, or intralesional.  
     
     
         14 . The method of  claim 13 , wherein the intralesional administration comprises perfusing or contacting a graft or organ with the 200 gene product before transplant.  
     
     
         15 . The method of  claim 2  wherein said administering of the nucleic acid is parenteral, subcutaneous, intraperitoneal, intrapulmonary, intranasal, or intralesional.  
     
     
         16 . The method of  claim 15 , wherein the intralesional administration comprises perfusing or contacting a graft or organ with the nucleic acid before transplant.  
     
     
         17 . The method of  claim 3  wherein said administering of the antibody is parenteral, subcutaneous, intraperitoneal, intrapulmonary, intranasal, or intralesional.  
     
     
         18 . The method of  claim 17 , wherein the intralesional administration comprises perfusing or contacting a graft or organ with the antibody before transplant.  
     
     
         19 . The method of  claim 3 , wherein the amount of the antibody administered is from about 1 μg/kg to about 100 mg/kg.  
     
     
         20 . The method of  claim 19 , wherein the amount of the antibody administered is from about 1 μg/kg to about 15 mg/kg.  
     
     
         21 . The method of  claim 20 , wherein the amount of the antibody administered is from about 0.1 mg/kg to about 2.0 mg/kg.

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